137: Diabetes & Other Endocrine Disorders Flashcards
What are the two main types of diabetes and their characteristics?
- Type 1 diabetes: Insulin deficiency due to immune-mediated destruction of islet cells in the pancreas.
- Type 2 diabetes: Chronic hyperglycemia primarily due to end-organ insulin resistance and a progressive decrease in pancreatic insulin release associated with aging.
What are some skin conditions associated with diabetes?
Diabetes-associated skin conditions include:
- Diabetic thick skin
- Limited joint mobility
- Eruptive xanthomas
- Acanthosis nigricans
How does hyperglycemia affect collagen in diabetes?
Hyperglycemia leads to nonenzymatic glycosylation of structural and regulatory proteins, including collagen, resulting in the formation of advanced glycation end products (AGEs) that decrease the solubility and enzymatic digestion of cutaneous collagen.
What is acanthosis nigricans and its significance in diabetes?
Acanthosis nigricans is a skin condition linked to obesity and insulin resistance, and it serves as a prognostic indicator for developing Type 2 diabetes mellitus.
What are the clinical implications of macroangiopathy and microangiopathy in diabetes?
Macroangiopathy and microangiopathy contribute to cutaneous complications of diabetes by increasing vessel wall permeability, decreasing vascular responsiveness, and leading to diabetic ulcers and increased risk of infection and injury.
What characterizes Type 1 diabetes?
Insufficiency of insulin due to immune-mediated destruction of islet cells in the pancreas.
What is the primary cause of Type 2 diabetes?
Chronic hyperglycemia due to end-organ insulin resistance and decreased pancreatic insulin release.
What leads to the formation of advanced glycation end products (AGEs) in diabetes?
Hyperglycemia leads to nonenzymatic glycosylation of proteins, including collagen.
How does hyperinsulinemia contribute to cutaneous manifestations in diabetes?
It mediates abnormal epidermal proliferation, leading to conditions like acanthosis nigricans.
What role does macroangiopathy play in diabetes complications?
It contributes to increased vessel wall permeability and predisposes patients to diabetic ulcers.
What is the relationship between lower-extremity vibratory perception and leg amputation risk in diabetes?
Those lacking vibratory perception have a 15.5 times increased probability of leg amputation.
What are the primary cutaneous manifestations of diabetes mellitus?
Manifestations include Acanthosis Nigricans, Limited Joint Mobility, Necrobiosis Lipoidica, Eruptive Xanthomas, and Bullous Diabeticorum.
What are the clinical features of acanthosis nigricans?
- Presents as brown to gray-black papillomatous cutaneous thickening in flexural areas (posterolateral neck, axillae, groin, abdominal folds).
- Distribution is usually symmetric with a dirty, velvety texture.
- Oral, esophageal, pharyngeal, laryngeal, conjunctival, and anogenital mucosal surfaces may be involved.
- Back of the neck is the most consistently and severely affected area.
- Development of superimposed acrochordons in involved areas.
- In florid cases, (+) involvement on the back of the hands and palms (tripe palms).
What are the potential causes of acanthosis nigricans?
- Loss-of-function mutations in the insulin receptor or anti-insulin receptor antibodies (Type A and Type B syndrome).
- Excess growth factor stimulation in the skin leading to aberrant proliferation of keratinocytes and fibroblasts.
- Insulin resistance and hyperinsulinemia may result from excess insulin binding to IGF1 receptors on keratinocytes and fibroblasts.
- Genetic syndromes (Crouzon and SADDAN) with mutations in fibroblast growth factor receptor 3.
- Drugs that can cause acanthosis nigricans include systemic glucocorticoids, nicotinic acid, and estrogens such as diethylstilbestrol.
What management strategies are recommended for acanthosis nigricans?
- Calcipotriol, salicylic acid, glycolic acid peels, urea, systemic, and topical retinoids have anecdotal success.
- Long-pulsed alexandrite laser treatment.
- Treatment of the underlying cause may be beneficial.
- Weight loss in obese patients.
- Medications that improve insulin sensitivity, such as metformin.
- In cases associated with malignancy, treat the underlying malignancy, often gastric in origin.
What are the clinical features of Limited Joint Mobility (LJM) and Scleroderma-like syndrome in diabetes?
- Presents as tightness and thickening of the skin and periarticular connective tissue of the fingers, resulting in a painless loss of joint mobility.
- Initial involvement of the DIP joints of the 5th digit usually progresses to involve all fingers.
- Larger joints of the elbow, knee, and foot may be affected.
- Characterized by the ‘prayer sign’ (inability to approximate palmar surfaces with hands pressed together).
- Skin may appear thickened, waxy, and smooth with apparent loss of adnexa, resembling scleroderma.
What is the epidemiology of Limited Joint Mobility (LJM) in diabetes?
- Of adult patients with Type 1 diabetes, 30% to 50% have LJM.
- It is also common in Type 2 diabetes.
What is the most important factor in diagnosing acanthosis nigricans?
Hyperinsulinemia.
What genetic mutations are associated with acanthosis nigricans?
Loss-of-function mutations in the insulin receptor or anti-insulin receptor antibodies (Type A and Type B syndrome).
What is the management approach for acanthosis nigricans associated with malignancy?
Treat the underlying malignancy, which is often a tumor of intraabdominal origin, usually gastric.
What is the clinical presentation of limited joint mobility (LJM) in diabetes?
It presents as tightness and thickening of the skin and periarticular connective tissue of the fingers, resulting in a painless loss of joint mobility.
What is the significance of the ‘prayer sign’ in patients with limited joint mobility?
It indicates an inability to approximate the palmar surfaces and interphalangeal joint spaces with the hands pressed together and fingers separated.
What is the relationship between scleroderma-like syndrome and diabetes?
Scleroderma-like syndrome is not associated with systemic sclerosis but correlates with the duration of diabetes and severity of joint contractures.
What treatments are recommended for diabetic thick skin?
Tight control of blood glucose and physical therapy to preserve active range of motion.
A patient with diabetes has a painless loss of joint mobility and thickened, waxy skin on the fingers. What is the condition, and what is the primary treatment?
The condition is Limited Joint Mobility (LJM). The primary treatment is intensive insulin therapy to control blood glucose, along with physical therapy to preserve range of motion.
What is the pathogenesis of Acanthosis Nigricans in insulin resistance?
In insulin resistance, excess insulin binds to IGF1 receptors on keratinocytes and fibroblasts, causing aberrant proliferation.
What are the clinical features of Acanthosis Nigricans, and what is its most consistently affected area?
Features include brown to gray-black papillomatous cutaneous thickening in flexural areas, with the back of the neck being the most consistently affected area.
What are the clinical features and pathogenesis of Acanthosis Nigricans?
Features include brown to gray-black papillomatous thickening in flexural areas. Pathogenesis involves excess insulin binding to IGF1 receptors, causing keratinocyte and fibroblast proliferation.
What is the epidemiology of Scleroderma Diabeticorum in patients with diabetes?
Affects 2.5% to 14% of patients with diabetes, particularly associated with longstanding diabetes and obesity among patients with Type 2 diabetes.
What are the clinical features of Scleroderma Diabeticorum?
- Insidious onset of painless, symmetric induration and thickening of the skin on the upper back and neck.
- May spread to the face, shoulders, and anterior torso.
- Skin retains a nonpitting, woody, peau d’orange quality.
- Associated with postinfectious scleredema and may lead to decreased sensation and range of motion.
What is the management approach for Scleroderma Diabeticorum?
- Radiotherapy
- Low-dose methotrexate
- Bath psoralen and ultraviolet A light (PUVA)
- Extracorporeal photopheresis
- Weight reduction and physical therapy
What are the clinical features of Eruptive Xanthomas?
- Present as 1-mm to 4-mm, reddish-yellow papules on the buttocks and extensor surfaces of the extremities.
- Lesions may coalesce into plaques over time.
- Often associated with severe hypertriglyceridemia and potentially undiagnosed diabetes.
What is the management for Eruptive Xanthomas?
- Lifestyle modification and control of the underlying diabetes.
- Lesions respond rapidly and usually resolve completely in 6 to 8 weeks.
What are the common skin infections in diabetic patients?
- Diabetic patients experience several skin infections more commonly and with greater severity.
- Leukocyte chemotaxis, adherence, and phagocytosis are impaired, especially during hyperglycemia and diabetic acidosis.
What is the epidemiology of diabetic ulcers?
- Occurs in 15% to 25% of diabetic patients.
- 10-30x increased risk of lower-extremity amputation.
- Lower-extremity ulcers account for 25% of all hospital stays for patients with diabetes.
What are the clinical features of diabetic ulcers?
- Callus formation precedes necrosis and breakdown of tissue over bony prominences of feet.
- Ulcers are surrounded by a ring of callus and may extend to underlying joint and bone.
- Complications include soft-tissue infection and osteomyelitis.
What are the major factors contributing to the development of diabetic ulcers?
- Peripheral neuropathy, pressure, and trauma.
- Neuropathy associated with uncontrolled hyperglycemia is a major predictor.
- Charcot arthropathy and ill-fitting shoes are common causes.
What percentage of patients with diabetes are affected by Scleroderma Diabeticorum?
2.5% to 14%.
What is a common cause of eruptive xanthomas?
Uncontrolled diabetes leading to severe hypertriglyceridemia.
What is the risk of lower-extremity ulcers in diabetic patients?
Occurs in 15% to 25% of diabetic patients with a 10-30x increased risk of lower-extremity amputation.
What are the complications associated with diabetic ulcers?
Soft-tissue infection and osteomyelitis.
What role does neuropathy play in diabetic ulcers?
Neuropathy is a major predictor of diabetic ulcers, especially when associated with uncontrolled hyperglycemia.
What factors are associated with foot ulceration in diabetes?
Previous foot ulceration, prior lower-extremity amputation, long duration of diabetes, impaired visual acuity, onychomycosis, and poor glycemic control.
How does the skin quality appear in Scleroderma Diabeticorum?
The skin retains a nonpitting, woody, peau d’orange quality.
What is the typical resolution time for eruptive xanthomas with management?
They usually resolve completely in 6 to 8 weeks.
A patient presents with painless, symmetric induration and thickening of the skin on the upper back and neck. What is the likely diagnosis, and what are the associated management strategies?
The likely diagnosis is Scleredema Diabeticorum. Management includes radiotherapy, low-dose methotrexate, bath PUVA, extracorporeal photopheresis, weight reduction, and physical therapy.
A patient with diabetes develops reddish-yellow papules on the buttocks and extensor surfaces of the extremities. What is the condition, and what is the underlying cause?
The condition is Eruptive Xanthomas, caused by severe hypertriglyceridemia, often associated with uncontrolled diabetes.
What are the key factors contributing to the development of diabetic ulcers?
Key factors include peripheral neuropathy, pressure, trauma, ill-fitting shoes, and socks. Neuropathy associated with uncontrolled hyperglycemia is a major predictor.
What are the clinical features and management of diabetic ulcers?
Features include callus formation, necrosis, and tissue breakdown over bony prominences. Management includes debridement, off-loading, and glycemic control.
What are the clinical features and management of Scleredema Diabeticorum?
Features include symmetric induration and thickening of the skin on the upper back and neck. Management includes weight reduction, physical therapy, and PUVA.
What are the clinical features and management of Eruptive Xanthomas?
Features include reddish-yellow papules on the buttocks and extensor surfaces, often asymptomatic but associated with severe hypertriglyceridemia. Management involves lifestyle modification and diabetes control.
What are the standard therapies for neuropathic diabetic ulcers?
Standard therapies include:
- Debridement
What is the management of Scleredema Diabeticorum?
Management includes weight reduction, physical therapy, and PUVA.
What are the clinical features of Eruptive Xanthomas?
Features include reddish-yellow papules on the buttocks and extensor surfaces, often asymptomatic but associated with severe hypertriglyceridemia.
What is the management of Eruptive Xanthomas?
Management involves lifestyle modification and diabetes control.
What are the standard therapies for neuropathic diabetic ulcers?
Standard therapies include debridement, off-loading, moist wound care, protective dressings, recombinant platelet-derived growth factor, and biologic approaches for large or poorly responsive ulcers.
What is the significance of glycemic control in preventing diabetic ulcers?
Optimizing glycemic control is crucial as it prevents neuropathy, which is closely associated with foot ulceration.
What are the clinical features of Necrobiosis Lipoidica?
Clinical features include sharply demarcated yellow-brown plaques on the anterior pretibial region, violaceous irregular borders, early presentation as red-brown papules and nodules, and ulceration in approximately 13% to 35% of cases.
What management strategies are recommended for Granuloma Annulare in diabetic patients?
Management strategies include early application of potent topical glucocorticoids, intralesional injection of glucocorticoids, short-term systemic glucocorticoids, aspirin and dipyridamole, tumor necrosis factor inhibitors, topical retinoids, topical PUVA, and surgical excision as a last resort.
What is the mean age of onset for Necrobiosis Lipoidica?
Around 30 years, with women having three times more cases than men.
What is the association between Granuloma Annulare and diabetes?
Diabetes is present in 9.7% of patients with localized GA and 21% of patients with generalized GA.
What are the management strategies for Necrobiosis Lipoidica?
Management includes early application of topical glucocorticoids, intralesional injections, and prevention of ulcers.
What is the risk associated with intralesional injection of glucocorticoids for Necrobiosis Lipoidica?
It shows improvement but comes with the risk of ulceration.
What is the significance of foot examinations in diabetic patients?
Foot examinations should be done in every patient visit to detect loss of protective sensation.
What is the complication rate of ulceration in patients with a history of ulceration?
Patients have a high risk for reulceration, with rates of 34% at 1 year, 61% at 3 years, and 70% at 5 years.
What are the clinical features and management of diabetic ulcers?
Management includes debridement, off-loading, moist wound care, protective dressings, and optimizing glycemic control.
What are the clinical features and management of Necrobiosis Lipoidica?
Features include yellow-brown plaques with violaceous borders on the anterior pretibial region. Management includes topical glucocorticoids, intralesional injections, and ulcer prevention.
What are the clinical features and management of Granuloma Annulare in diabetes?
Features include annular plaques with central clearing, often on the extremities. Management includes topical or intralesional glucocorticoids.
What are the clinical features of atrophic tibial lesions associated with diabetes?
They present as small (<1 cm), atrophic, pink to brown, scar-like macules on the pretibial areas.
What is the management approach for individual atrophic tibial lesions in diabetes?
No treatment is necessary for individual atrophic tibial lesions as they are asymptomatic.
What are the characteristics of Bullous Diabeticorum?
Abrupt, spontaneous development of painless, non-pruritic blisters on the lower extremities, usually healing within 2 to 5 weeks.
What are the physiologic changes in the skin related to obesity?
Alterations in epidermal barrier function, increased sweating, larger skin folds, increased skin surface pH, poor lymphatic drainage, and impaired wound healing.
What are the contributing factors to the pathogenesis of obesity and metabolic syndrome?
Nutritional choices, activity/exercise, medications, inflammation, insulin resistance, depression, degenerative joint disease, obstructive sleep apnea, gonadal dysfunction, and vitamin D deficiency.
What is the relationship between the incidence of shin spots and diabetes?
The incidence of shin spots is correlated with the duration of diabetes and the presence of retinopathy, nephropathy, and neuropathy.
What characterizes acquired perforating disorders in diabetes?
They are characterized by transepidermal elimination or ‘spitting’ of altered dermal constituents.
What is the pathogenesis of diabetic bullae?
The pathogenesis is unknown, but the formation of advanced glycation end products (AGEs) may lead to increased fragility.
How is obesity defined in terms of body mass index (BMI)?
Obesity is defined as a BMI greater than 30 kg/m2, while overweight is defined as a BMI greater than 25.
What are some physiological changes in the skin related to obesity?
Physiological changes include alterations in epidermal barrier function, increased sweating, larger skin folds, and impaired wound healing.
What is the most important therapy for managing obesity and metabolic syndrome?
The most important therapy is weight reduction and exercise along with adequate control of cardiac risk factors.
What are the clinical features and management of Bullous Diabeticorum?
Clinical features include painless, non-pruritic bullae on the lower extremities. Management involves supportive treatment and ruling out other blistering diseases.
What is the role of leptin in regulating body weight and metabolism?
Leptin regulates energy homeostasis, neuroendocrine function, and metabolism.
What condition can leptin deficiency cause?
Extreme obesity, hyperphagia, diabetes, neuroendocrine abnormalities, and infertility.
What is the effect of leptin resistance in obese individuals?
They have high circulating levels of leptin, making pharmacologic leptin administration ineffective for weight loss.
What is the function of Ghrelin?
Ghrelin is a gastric-derived hormone that stimulates appetite and modulates body weight.
What is the most common cause of hyperthyroidism?
Graves disease, accounting for 60% to 80% of all cases.
What is the incidence of hypothyroidism in the U.S. population?
Hypothyroidism is present in 4.6% of the U.S. population.
What are common cutaneous changes associated with hyperthyroidism?
Soft, warm, and velvety skin texture.
What is thyroid dermopathy?
A classic manifestation of Graves disease, often associated with thyroid ophthalmopathy.
What is the significance of vitiligo in thyroid disease?
Vitiligo is overrepresented in patients with Graves disease and often predates the diagnosis.
What are the primary clinical features of hyperthyroidism-related cutaneous changes?
Features include soft, warm, and velvety skin, fine and soft scalp hair, and brittle nails.
What is the extreme form of diffuse thyroid dermopathy?
The extreme form is known as the elephantiasic variant, characterized by progressive thickening and gray-black hyperpigmentation of the pretibial skin.
What is the extreme form of diffuse thyroid dermopathy known as?
The extreme form of diffuse thyroid dermopathy is known as the elephantiasic variant. It occurs in less than 1% of patients with Graves’ disease and is characterized by progressive thickening and gray-black hyperpigmentation of the pretibial skin, accompanied by woody, firm edema with nodule formation.
What cutaneous condition is characterized by digital clubbing, soft-tissue swelling of the hands and feet, and the presence of characteristic periosteal reactions?
The cutaneous condition characterized by digital clubbing, soft-tissue swelling of the hands and feet, and the presence of characteristic periosteal reactions is known as thyroid acropachy. It is almost always associated with thyroid dermopathy and exophthalmos.
What are the cardiovascular effects of thyroid hormone excess on the skin?
The cardiovascular effects of thyroid hormone excess result in:
1. Increased blood flow to the skin, manifesting as facial flushing and palmar erythema.
2. An increase in metabolism, which, along with increased peripheral blood flow and temperature dysregulation, can lead to generalized hyperhidrosis.
3. A higher incidence of chronic urticaria in patients with thyroid disease.
What is the significance of hyperpigmentation in patients with hyperthyroidism?
Hyperpigmentation in patients with hyperthyroidism is characterized by increased pigment in the palmar creases, gingiva, and buccal mucosa, usually more prominent in individuals with darker skin. This hyperpigmentation is a result of increased corticotropin (ACTH) due to accelerated cortisol metabolism.
What is the cutaneous condition characterized by rugated appearance of the palmar surface usually associated with acanthosis nigricans in the setting of malignancy?
Acanthosis nigricans.
What condition presents with the insidious onset of painless, symmetric induration and thickening of the skin on the upper back and neck among diabetes mellitus patients?
Diabetic dermopathy.
What are three genes that serve as regulators of body adiposity?
Leptin, adiponectin, and resistin.
In acanthosis nigricans, what is the most consistently affected area?
The neck and axillae.
What sign indicates a patient is unable to approximate the palmar surface of the proximal and distal interphalangeal joints with palms pressed together?
LJM sign (Lateral Joint Mobility sign).
What gastric-derived, appetite-stimulating hormone regulates obesity?
Ghrelin.
What are the clinical features of thyroid dermopathy, and what is its most severe variant?
Thyroid dermopathy presents as painless, nonpitting nodules and plaques with a waxy, indurated texture, commonly on the extensor surfaces of the legs. The most severe variant is the elephantiasic form, characterized by progressive thickening and gray-black hyperpigmentation of the pretibial skin.
What are the clinical features of thyroid acropachy, and how is it diagnosed?
Features include digital clubbing, soft-tissue swelling of the hands and feet, and periosteal reactions. Diagnosis is aided by radiographic findings and bone scans.
What are the clinical features and management of thyroid dermopathy?
Features include painless, nonpitting nodules and plaques with a waxy texture, commonly on the legs. Management focuses on treating the underlying thyroid condition.
What are the clinical features and management of thyroid acropachy?
Features include digital clubbing and periosteal reactions. Management involves treating the underlying thyroid disease.
What are the risk factors for diabetic ulcers as outlined in the approach to care for diabetic foot and ulcers?
The risk factors for diabetic ulcers include:
- Elevated HbA1c
- Vision poorer than 20/40
- History of foot ulcer
- History of amputation
- Monofilament insensitivity
- Onychomycosis.
What is the initial step in managing a diabetic ulcer when it is present?
The initial step in managing a diabetic ulcer is to assess for palpable foot pulses. If pulses are present, further evaluation for clinical signs of cellulitis or osteomyelitis is conducted.
What should be done if clinical signs of cellulitis or osteomyelitis are present in a diabetic ulcer patient?
If clinical signs of cellulitis or osteomyelitis are present, the following actions should be taken:
1. Sharp debridement
2. Eliminate pressure
3. Consider osteomyelitis evaluation and begin appropriate antibiotics.
What are the follow-up actions if a diabetic ulcer shows improvement within 4 weeks?
If a diabetic ulcer shows improvement by 4 weeks, the follow-up actions include:
- Regular follow-up
- Education about foot care
- Addressing modifiable risk factors.
What should be assessed if there is no improvement in a diabetic ulcer after 4 weeks?
If there is no improvement in a diabetic ulcer after 4 weeks, the following should be assessed:
- Check compliance
- Reassess for infection
- Consider adjuvant care.
What should be done if an ulcer is present and there are clinical signs of cellulitis or osteomyelitis?
Perform sharp debridement and eliminate pressure.
What is the next step if a diabetic ulcer is present but there are no palpable foot pulses?
Conduct a noninvasive vascular assessment to check for clinically significant arterial obstruction.
What should be done if there is improvement in a diabetic ulcer by 4 weeks?
Continue with regular follow-up, education about foot care, and address modifiable risk factors.
What actions should be taken if there is no improvement in a diabetic ulcer by 4 weeks?
Check compliance, reassess for infection, and consider adjuvant care.
What are the characteristic facial changes associated with hypothyroidism?
Characteristic facial changes include:
- Broadened nose
- Thickened lips
- Puffy eyelids
- Macroglossia with a smooth and clumsy tongue
How does hypothyroidism affect hair growth and quality?
In patients with hypothyroidism, hair is:
- Coarse, dry, and brittle
- Slowed growth
- Alopecia can be either diffuse or patchy
- Increased numbers of hair follicles in telogen and telogen effluvium may occur when hypothyroidism onset is abrupt.
What is myxedema and how is it related to hypothyroidism?
Myxedema is a classic finding associated with hypothyroidism, characterized by:
- Dermal accumulation of mucopolysaccharides (hyaluronic acid and chondroitin sulfate)
- Tends to resolve with treatment of hypothyroidism
- Can be generalized but often appears more striking in the extremities.
What skin changes are observed in patients with hypothyroidism?
Skin changes in hypothyroidism include:
- Cool and pale skin due to decreased core temperature and increased peripheral vasoconstriction
- Xerotic skin with a poorly hydrated stratum corneum
- Hyperkeratosis with follicular plugging
- Yellow-orange discoloration due to beta-carotene accumulation, sparing the sclerae (pseudo-jaundice)
- Fine wrinkling of the skin
